The BA.2 COVID-19 variant maintained the mutations necessary for viral entry, but developed an increased ability to evade neutralization by monoclonal antibodies.
Even as it mutates, Omicron retains its status as the predominant COVID-19 variant. According to the Centers for Disease Control and Prevention (CDC), the BA.5 subvariant now accounts for 77.9% of cases in the US.
One study, published in the International Journal of Molecular Sciences, sought to gain insight into Omicron’s mutation profile and its impact on interactions with receptor and monoclonal antibodies.
“Throughout the pandemic, the virus has continued to get smarter and smarter,” said Dr. Kamlendra Singh, a professor at the University of Missouri College of Veterinary Medicine, Christopher S. Bond Life Sciences Center principal investigator, and study author. “Even with vaccines, it continues to find new ways to mutate and evade existing antibodies. Omicron now has more than 130 sublineages, and they have been here for quite a while. We are now just finally able to detect them and differentiate among them with this research.”
As of February 2022, the investigators analyzed 8660 available genomic sequences for the prevalence of the BA.2 mutation profile. They conducted molecular dynamics simulations to determine the structures of spike/receptor and spike/antibody complexes.
They analyzed available structures of spike receptor-binding domain (S-RBD) of the original COVID-19 strain, Wuhan-Hu-1, and Omicron strains in conjunction with monoclonal antibodies to understand the function of mutations at the interface.
The investigators found significant differences in the number and distribution of mutations between Omicron BA.1 and BA.2. BA.2 maintained the critical contacts with ACE2 necessary for viral entry, but evolved to further evade neutralization by monoclonal antibodies. “A combination of these two factors rendered BA.2 an alarming variant that could impact current and future vaccination strategies,” the study authors wrote.
BA.2 has 50 high-prevalent mutations, compared to 48 in BA.1. There were 17 BA.1 mutations not present in BA.2, replaces by 19 unique mutations and the signature Delta mutation G142D. BA.2 had 28 signature spike mutations, while BA.1 had 30. This is because BA.2 had 2 revertant mutations, S446G and S496G, in its RBD. This revertant mutations make BA.2 somewhat similar to Wuhan-Hu-1, although BA.2’s RBD was more stable than the parent strain.
The investigators concluded that BA.2 had evolved with novel mutations to maintain receptor binding similar to the original COVID-19 strain, evade antibody binding even more successfully than BA.1, and acquire a mutation similar to Delta that may be the source of high infectivity.
Singh noted that people who have been vaccinated or “naturally” infected may have generated protective antibodies against some variants, but these may be rendered ineffective as Omicron continues to mutate. “The various mutations may seem like only subtle differences,” he said, “but they are very important.”